Host immune response determines visceral hyperalgesia in a rat model of post-inflammatory irritable bowel syndrome

Irritable bowel syndrome (IBS) is associated with visceral hyperalgesia and frequently occurs after a transient gastrointestinal infection. Only a proportion of patients with acute gastroenteritis develop post-infectious IBS suggesting differences in host response to inflammatory stimuli. We aimed to investigate this concept by characterizing visceral sensitivity in two rat strains, following a chemically induced colitis. Colorectal instillation of trinitrobenzenesulfonic acid (TNBS) in aqueous ethanol was used to induce a transient colitis in Lewis and F344 rats. The colitis was characterized semiquantitatively by histology, as well as by quantitative methods using Tc-99m-leukocytes (radioactive organ assay) and plasma IL-2 and IL-6 levels. Visceromotor response to colorectal distensions was assessed after 2 h and, 5, 14, and 28 days. The colitis peaked on day 5 and dissipated to no visible mucosal damage on day 14. Cytokines were significantly increased in TNBS-treated rats at 2 h and on day 5. On day 14 cytokines were still significantly enhanced in Lewis but not Fisher rats. Both strains had a highly inflamed to non-inflamed tissue ratio at 3 h after TNBS instillation with increased uptake in Lewis compared to F344 rats. No Tc-99m-tin-colloid-leukocytes were detected in colon samples on day 28. Visceromotor response was significantly elevated in both strains during the acute colitis (day 5), whereas only Lewis rats developed a post-inflammatory (day 28) visceral hyperalgesia. Genetically determined host factors account for prolonged immune activation in response to a standardized inflammatory stimulus and are linked to susceptibility for a post-inflammatory visceral hyperalgesia.